Regulatory effect of lysophosphatidic acid on lymphocyte migration

Lysophosphatidic acid (LPA) is a lipid mediator that is known to exhibit chemotactic activity toward a variety of cancer cells. However, its effect on the immune system has not been studied extensively. Another lipid mediator, sphingosine-1-phosphate (S1P), has been shown to influence lymphocyte recirculation by regulating lymphocyte egress from lymphoid organs. In this study, we found that LPA inhibits spontaneous migration of mouse splenic lymphocytes through a chemorepulsive effect. We also demonstrated that LPA inhibits chemokine CCL21-induced lymphocyte migration. This inhibitory effect on CCL21-induced migration was observed for both T and B cells. The involvement of a receptor, LPA(1), LPA(2) or LPA(3), in the inhibition of the CCL21-induced migration was confirmed with a synthetic agonist, oleyl thiophosphate. Considering that the signaling by CCL21 through cognate receptor CCR7 contributes to lymphocyte homing and dendritic cell trafficking to lymph nodes, LPA may play a role as a key regulator of these processes. The inhibitory effect of LPA is in remarkable contrast to the effect of S1P receptor signaling, which is known to potentiate lymphocyte chemotaxis involving CCR7.